The present volume of Epigenetics and Human Health is devoted to the patho-epigenetics of viral and microbial infections, an exiting new field of disease-related epigenetic research. As recognized during the past years, epigenetic reprogramming of pathogen and host genome functions - the latter frequently induced by pathogens - plays an important role in many infectious processes. Beyond their immediate relevance for pathogen proliferation and obligatorily associated symptoms, such alterations frequently contribute to severe additional complications, such as the development of immunodeficiency, cancer and various chronic disorders. This holds in particular for epigenetic dysregulation of host gene expression induced by latent infections. The present book summarizes current knowledge of the mechanisms underlying epigenetic changes caused by viral, bacterial, fungal and protozoan infections and their impact on human health.

The present volume of Epigenetics and Human Health is devoted to the patho-epigenetics of viral and microbial infections, an exiting new field of disease-related epigenetic research. As recognized during the past years, epigenetic reprogramming of pathogen and host genome functions - the latter frequently induced by pathogens - plays an important role in many infectious processes. Beyond their immediate relevance for pathogen proliferation and obligatorily associated symptoms, such alterations frequently contribute to severe additional complications, such as the development of immunodeficiency, cancer and various chronic disorders. This holds in particular for epigenetic dysregulation of host gene expression induced by latent infections. The present book summarizes current knowledge of the mechanisms underlying epigenetic changes caused by viral, bacterial, fungal and protozoan infections and their impact on human health.

For decades this virus system has served--and continues to do so--to pioneer investigations on the molecular biology, biochemistry and genetics of mammalian cell systems. This three volume work presents an up-to-date account of recent basic research in one of the most important experimental systems for biochemical, cell biological, genetic, virological and epidemiological investigations in mammalian molecular biology. In this, the second of three volumes, the attention is turned to such topics as DNA replication, recombination and integration, and post-transcriptional control. The chapters have been written by an international group of leading experts in their respective fields of interest.

For decades this virus system has served--and continues to do so--to pioneer investigations on the molecular biology, biochemistry and genetics of mammalian cell systems. This three volume work presents an up-to-date account of recent basic research in one of the most important experimental systems for biochemical, cell biological, genetic, virological and epidemiological investigation in mammalian molecular biology. In the first of the three volumes, we present an overview of adenovirus research. In the second volume, we turn our attention to such topics as DNA replication, recombination and integration and post-trans- criptional control. This, the third volume then looks at transformation and E1A, adenovirus genetics, pathogenesis and gene therapy.

For decades this virus system has served - and continues to do so - to pioneer investigations on the molecular biology, biochemistry and genetics of mammalian cell systems. This three volume work presents an up-to-date account of recent basic research in one of the most important experimental systems for biochemical, cell biological, genetic, virological, and epidemiological investigations in mammalian molecular biology. In this, the first of the three volumes, an overview of adenovirus research is presented with emphasis on the structure and assembly of adenoviruses, viral infections, and viral gene products. The chapters have been written by an international group of leading experts in their respective fields of interest.

The pathology caused by baculoviruses in insect popula- tions was described centuries ago, notably in the larvae of insects such as the silkworm (Bombyx mori) which has been appreciated for the quality and beauty of its products. In the 1940s baculoviruses and their structure and physiolo- gy were intensively investigated, particularly by Bergold's group in Tiibingen. The following decades saw excellent progress, laying a solid virological base for later investiga- tions on the system. Further studies mushroomed in the 1970s with the advent of tissue culture systems for insect cells which eventually facilitated the molecular biological approach that came to the fore in the 1980 s. One of the reasons for pursuing research on the baculo- virus system was the prospect of eventually using these vi- ruses as insect pest control agents. While this practical as- pect may appeal to many, molecular biologists had addi- tional reasons to be interested in baculoviruses. Here was a large DNA viral genome, probably fraught with problems of replication and regulation that hopefully would open inroads into the molecular biology of interesting insect cell systems. In the days when genetechnology promises laurels, and after several virus systems had been skilfully exploited as highly efficient eukaryotic expression vectors, it came as no surprise that baculoviruses were also investigated in that respect. Indeed, the Autographa californica nuclear po- lyhedrosis virus became a good vector. Insect cells also seem to collaborate in modifying and processing the gene- technologically synthesized polypeptides.

It has become apparent that the genomes of many organisms are characterized by unique patterns of DNA methylation which can differ from genome segment to genome segment and cell type to cell type. These patterns can be instrumental in determining cell type and function. Thus, it is not surprising that studies on the role of DNA methylation now occupy center stage in many fields of biology and medicine such as developmental biology, genetic imprinting, genetic disease, tumor biology, gene therapy, cloning of organisms and others. Once again, basic research in molecular biology has provided the essential foundation for investigations of biomedical problems.

It has become apparent that the genomes of many organisms are characterized by unique patterns of DNA methylation which can differ from genome segment to genome segment and cell type to cell type. These patterns can be instrumental in determining cell type and function. Thus, it is not surprising that studies on the role of DNA methylation now occupy center stage in many fields of biology and medicine such as developmental biology, genetic imprinting, genetic disease, tumor biology, gene therapy, cloning of organisms and others. Once again, basic research in molecular biology has provided the essential foundation for investigations of biomedical problems.

2 On the Early History of 5-mC In the fall of 1966, Norton D. Zinder of Rockefeller University in New York City presented the Harvey Lecture on "Phage RNA as Genetic Material" (Zinder 1966). Frankly,I do not remember manydetailsofhis talk. However, one ofhis concluding remarks, in which he thanked his teacher Rollin Hotchkiss, stuck in my mind andbecame an important leitmotiffor much of my own scienti?c career. Norton's relevant passages went somethinglikethis (approximate quotation): When we hope to have made a scienti?c discovery, we better spend much of our time immediately after this fortunate event in trying to counter our own beliefsand interpretations. Onlyafter a lot of painstaking scrutiny involving many control experiments when our discoveryhas stood the test of careful consideration, can one hope that our colleagues will beabletocon?rm the new ?ndings. Of course, it is a major task of the scienti?c community to respectfully meet supposedly novel announ- ments withdisbelief and skepticism and in turn commence the process of disproving these concepts. Consistent con?rmations, with plenty of modi?cations to be sure, will providethe encouragement necessary to continue and to improve the initial observations and conclusions. Apparently, the scienti?c tradition re?ected in this overall cautious attitude had emanatedfrom the laboratory of Oswald Avery that Rollin Hotchkiss had been trained in. This certainly most important of scienti?ccredos seems tocontradict intuitively held notions and might bethought to run counter to general practice.

After three volumes on adenoviruses in 1995 the past years have seen rapid progress in the field of adenovirus research. Moreover, adenoviruses have attracted considerable interest as vectors in gene transfer regimens. After the first volume on virion and structure, viral replication and host-cell interaction this second volume deals with the immune system, oncogenesis and gene therapy.

Although adenoviruses have been established for quite some time as one of the most pliable tools to study the molecular biology of mammalian cells, rapid progress continues to be made with this virus system. The adenoviral genome introduced into the nucleus of cells as a Trojan Horse, as it were, is now facili- tating investigators to uncover details of cellular mechanisms. In this volume twelve chapters have been collected that summarize important current research on different mechanisms in adenovirus- infected and -transformed cells. It has become increasingly apparent that some of these mechanisms do not only pertain to highly specialized strategies of the viral genome and its expres- sion or replication, but may simultaneously shed light on events indigenous to the cell. "Adenovirus DNA: The Viral Genome and its Expression" high- lights the first publication of the entire annotated sequence of 35. 937 nucleotide pairs of adenovirus type 2 DNA by the Cold Spring Harbor and Uppsala groups (chapter 1). Goran Akusjarvi, Ulf Pettersson (Uppsala University) and Rich Roberts (Cold Spring Harbor) present a survey on the structure and function of the adenovirus-2 genome (chapter 2). A considerable amount of in- formation has been collected on the biochemical mechanisms in- vol ved in adenov irus DNA repl ication in human cells. Al though highly specialized in the way of initiating DNA replication, adenov irus DNA repl ication represents probably one of the best studied systems in work on eukaryotic DNA replication.

Autorenportrait: Prof. Dr. Walter Doerfler, geb. 1933, studierte Medizin und schloss daran eine Ausbildung in Biochemie und Molekularbiologie an. Langjahrige Tatigkeit an verschiedenen Universitaten in den USA, seit 1972 Professor fur Genetik an der Universitat zu Koln. Seine Hauptarbeitsgebiete sind die DNA-Viren, die Aufnahme von fremder DNA in das Erbgut von Saugern und Probleme der medizinischen Genetik."